Long-term imaging of cellular forces with high precision by elastic resonator interference stress microscopy

This project has received funding from the Human Frontiers Science Program (RGY0074/2013), the Scottish Funding Council (via SUPA), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 640012), the EPSRC DTP (EP/L505079/1), the RS MacDonald Charitable Trust and the MRC (G1100116 and G110312/1).Cellular forces are crucial for many biological processes but current methods to image them have limitations with respect to data analysis, resolution and throughput. Here, we present a robust approach to measure mechanical cell–substrate interactions in diverse biological systems by interferometrically detecting deformations of an elastic micro-cavity. Elastic resonator interference stress microscopy (ERISM) yields stress maps with exceptional precision and large dynamic range (2 nm displacement resolution over a >1 μm range, translating into 1 pN force sensitivity). This enables investigation of minute vertical stresses (<1 Pa) involved in podosome protrusion, protein-specific cell–substrate interaction and amoeboid migration through spatial confinement in real time. ERISM requires no zero-force reference and avoids phototoxic effects, which facilitates force monitoring over multiple days and at high frame rates and eliminates the need to detach cells after measurements. This allows observation of slow processes such as differentiation and further investigation of cells, for example, by immunostaining.PostprintPeer reviewe

High electron mobility in AlGaN/GaN heterostructures grown on bulk GaN substrates

Dislocation-free high-quality AlGaN/GaN heterostructures have been grown by molecular-beam epitaxy on semi-insulating bulk GaN substrates. Hall measurements performed in the 300 K–50 mK range show a low-temperature electron mobility exceeding 60 000 cm2/V s for an electron sheet density of 2.4×1012 cm−2. Magnetotransport experiments performed up to 15 T exhibit well-defined quantum Hall-effect features. The structures corresponding to the cyclotron and spin splitting were clearly resolved. From an analysis of the Shubnikov de Hass oscillations and the low-temperature mobility we found the quantum and transport scattering times to be 0.4 and 8.2 ps, respectively. The high ratio of the scattering to quantum relaxation time indicates that the main scattering mechanisms, at low temperatures, are due to long-range potentials, such as Coulomb potentials of ionized impurities

Mammographic density and epithelial histopathologic markers

<p>Abstract</p> <p>Background</p> <p>We explored the association of mammographic density, a breast cancer risk factor, with hormonal and proliferation markers in benign tissue from tumor blocks of pre-and postmenopausal breast cancer cases.</p> <p>Methods</p> <p>Breast cancer cases were recruited from a case-control study on breast density. Mammographic density was assessed on digitized prediagnostic mammograms using a computer-assisted method. For 279 participants of the original study, we obtained tumor blocks and prepared tissue microarrays (TMA), but benign tissue cores were only available for 159 women. The TMAs were immunostained for estrogen receptor alpha (ERα) and beta (ERβ), progesterone receptor (PR), HER2/neu, Ki-67, and Proliferating Cell Nuclear Antigen (PCNA). We applied general linear models to compute breast density according to marker expression.</p> <p>Results</p> <p>A substantial proportion of the samples were in the low or no staining categories. None of the results was statistically significant, but women with PR and ERβ staining had 3.4% and 2.4% higher percent density. The respective values for Caucasians were 5.7% and 11.6% but less in Japanese women (3.5% and -1.1%). Percent density was 3.4% higher in women with any Ki-67 staining and 2.2% in those with positive PCNA staining.</p> <p>Conclusion</p> <p>This study detected little evidence for an association between mammographic density and expression of steroid receptors and proliferation markers in breast tissue, but it illustrated the problems of locating tumor blocks and benign breast tissue samples for epidemiologic research. Given the suggestive findings, future studies examining estrogen effects in tissue, cell proliferation, and density in the breast may be informative.</p

Use of SU8 as a stable and biocompatible adhesion layer for gold bioelectrodes.

Gold is the most widely used electrode material for bioelectronic applications due to its high electrical conductivity, good chemical stability and proven biocompatibility. However, it adheres only weakly to widely used substrate materials such as glass and silicon oxide, typically requiring the use of a thin layer of chromium between the substrate and the metal to achieve adequate adhesion. Unfortunately, this approach can reduce biocompatibility relative to pure gold films due to the risk of the underlying layer of chromium becoming exposed. Here we report on an alternative adhesion layer for gold and other metals formed from a thin layer of the negative-tone photoresist SU-8, which we find to be significantly less cytotoxic than chromium, being broadly comparable to bare glass in terms of its biocompatibility. Various treatment protocols for SU-8 were investigated, with a view to attaining high transparency and good mechanical and biochemical stability. Thermal annealing to induce partial cross-linking of the SU-8 film prior to gold deposition, with further annealing after deposition to complete cross-linking, was found to yield the best electrode properties. The optimized glass/SU8-Au electrodes were highly transparent, resilient to delamination, stable in biological culture medium, and exhibited similar biocompatibility to glass

Die monistische Weltanschauung

dargest. u. geprüft von E. G. Steud